Compositions and methods of applying alternating electric fields to pluripotent stem cells

Abstract

Disclosed are methods and compositions for preventing or disrupting mitosis of pluripotent stem cells, killing pluripotent stem cells, preventing or disrupting division of pluripotent stem cells, reducing the viability of pluripotent stem cells, slowing the progression or differentiation of pluripotent stem cells, and treating an ectopic pregnancy.

We claim: 
     
         1 . A method of preventing or disrupting mitosis of a pluripotent stem cell comprising:
 a. exposing the pluripotent stem cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field prevents or disrupts mitosis of the pluripotent stem cells.   
     
     
         2 . A method of killing a pluripotent stem cell comprising:
 a. exposing the pluripotent stem cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field mitosis kills the pluripotent stem cell.   
     
     
         3 . A method of preventing or disrupting division of a pluripotent stem cell comprising:
 a. exposing the pluripotent stem cells to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field prevents or disrupts division of the pluripotent stem cell.   
     
     
         4 . A method of reducing the viability of a pluripotent stem cell comprising:
 a. exposing the pluripotent stem cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field reduces viability of the pluripotent stem cell.   
     
     
         5 . A method of slowing the progression of a pluripotent stem cell comprising:
 a. exposing the pluripotent stem cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field slows the progression of the pluripotent stem cell.   
     
     
         6 . A method of preventing or disrupting mitosis of pluripotent stem cells in a target site of a subject, comprising
 a. applying an alternating electric field to the target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field in the target site of the subject prevents or disrupts mitosis of the pluripotent stem cells in the target site.   
     
     
         7 . A method of killing pluripotent stem cells in a target site of a subject, comprising
 a. applying an alternating electric field to the target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field in the target site of the subject kills the pluripotent stem cells in the target site.   
     
     
         8 . A method of preventing or disrupting division of pluripotent stem cells in a target site of a subject, comprising
 a. applying an alternating electric field to the target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field in the target site of the subject prevents or disrupts division of the pluripotent stem cells in the target site.   
     
     
         9 . A method of reducing the viability of pluripotent stem cells in a target site of a subject, comprising
 a. applying an alternating electric field to the target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field in the target site of the subject reduces viability of the pluripotent stem cells in the target site.   
     
     
         10 . A method of slowing the progression or differentiation of pluripotent stem cells in a target site of a subject, comprising
 a. applying an alternating electric field to the target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   wherein the frequency and field strength of the alternating electric field in the target site of the subject slows the progression or differentiation of the pluripotent stem cells in the target site.   
     
     
         11 . The method of  any of the preceding claims , wherein the pluripotent stem cells are fetal stem cells, embryonic stem cells or induce pluripotent stem cells. 
     
     
         12 . The method of any of  claims 6-10 , wherein the target site is in a fallopian tube or on a cesarean scar of the subject. 
     
     
         13 . The method of  any of the preceding claims , further comprising administering gefitinib, methotrexate, or a combination thereof to the subject. 
     
     
         14 . The method of  any of the preceding claims , wherein the subject is pregnant. 
     
     
         15 . The method of  any of the preceding claims , wherein the subject has elevated levels of human chorionic gonadotropin (HCG). 
     
     
         16 . The method of  any of the preceding claims , wherein the subject has been identified to have elevated levels of human chorionic gonadotropin (HCG). 
     
     
         17 . The method of  any of the preceding claims , wherein the subject has been identified to have an abnormal pattern in the rise of levels of human chorionic gonadotropin (HCG). 
     
     
         18 . The method of  any of the preceding claims , wherein the subject has been diagnosed with an ectopic pregnancy. 
     
     
         19 . The method of  any of the preceding claims , wherein the subject has been identified to have elevated levels of human chorionic gonadotropin (HCG). 
     
     
         20 . The method of  any of the preceding claims , wherein the subject has been identified to have an abnormal pattern in the rise of levels of human chorionic gonadotropin (HCG). 
     
     
         21 . The method of  any of the preceding claims , wherein the subject has been identified or diagnosed via (transvaginal) ultrasound. 
     
     
         22 . The method of  any of the preceding claims , wherein the method further comprises observation, laparoscopy, laparotomy, or medication. 
     
     
         23 . The method of  any of the preceding claims , further comprising administering gefitinib, methotrexate, or a combination thereof to the subject. 
     
     
         24 . The method of  any of the preceding claims , further comprising:
 a. introducing a nanoparticle to a target site in the subject; and   b. applying an alternating electric field to the target site of the subject,   wherein the electric impedance in the target site of the subject to the alternating current is altered.   
     
     
         25 . The method of  claim 24 , wherein the current density and/or power loss density in the target site of the subject to the alternating current is altered. 
     
     
         26 . The method of  claim 24 , wherein the nanoparticle is a conductive nanoparticle. 
     
     
         27 . The method of  claim 24 , wherein the impedance in the target site is lowered. 
     
     
         28 . The method of  claim 24 , wherein the conductivity in the target site is increased. 
     
     
         29 . The method of  claim 24 , wherein the nanoparticle is a non-conductive nanoparticle. 
     
     
         30 . The method of  claim 29 , wherein the impedance in the target site is increased. 
     
     
         31 . The method of any of  claims 29-30 , wherein the conductivity in the target site is decreased. 
     
     
         32 . The method of any of  claims 24-31 , wherein the alternating electric field is a tumor-treating field. 
     
     
         33 . The method of  claim 24 , wherein the nanoparticles are nanoparticles that increase tissue permittivity. 
     
     
         34 . The method any of  claims 24-33 , wherein the efficacy of the alternating electric field in the target site of the subject is increased. 
     
     
         35 . The method any of  claims 24-33 , wherein the magnitude of the current density of the alternating electric field is increased in the target site. 
     
     
         36 . The method any of  claims 34-35 , wherein the increased efficacy of the alternating electric field in the target site results in an increased anti-mitotic effect of the alternating electric field in the target site. 
     
     
         37 . The method any of  claims 24-36 , wherein of  any of the preceding claims , wherein the nanoparticle is introduced into the embryonic cell or pluripotent stem cell. 
     
     
         38 . A method of treating ectopic pregnancy comprising:
 a. applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength,   b. wherein the target site comprises an ectopic pregnancy.   
     
     
         39 . A device for effectively preventing or disrupting mitosis of pluripotent stem cells, killing pluripotent stem cells, preventing or disrupting division of pluripotent stem cells, reducing the viability of pluripotent stem cells, slowing the progression or differentiation of pluripotent stem cells, or treating an ectopic pregnancy. 
     
     
         40 . A device including: a signal generator; a temperature sensor electrically connected to the signal generator; and a pair of electrodes which receive an AC voltage from the signal generator, wherein the signal generator is configured to generate an electric field between the pair of electrodes so as to change orientations of a nanoparticle inside a pluripotent stem cell, the temperature sensor measures a temperature around the pluripotent stem cell, and the signal generator is configured to change an intensity of the electric field on the basis of the measured temperature. 
     
     
         41 . A device including: a signal generator; a temperature sensor electrically connected to the signal generator; and a pair of electrodes which receive an AC voltage from the signal generator, wherein the signal generator is configured to generate an electric field between the pair of electrodes so as to change orientations of a nanoparticle adjacent to a pluripotent stem cell, the temperature sensor measures a temperature around the pluripotent stem cell, and the signal generator is configured to change an intensity of the electric field on the basis of the measured temperature. 
     
     
         42 . The device of  claim 40 or 41 , wherein the electric field has a frequency of about 100 KHz to about 500 KHz. 
     
     
         43 . The device of  claim 40 , wherein the nanoparticles are conductive nanoparticles. 
     
     
         44 . The device of any of  claims 41-42 , wherein the nanoparticles are nonconductive nanoparticles. 
     
     
         45 . The device of  claim 44 , wherein the nonconductive nanoparticles are ferroelectric nanoparticles. 
     
     
         46 . The device of  claim 45 , wherein the ferroelectric particles have diameters of greater than about 0 nm to ≤about 50 nm. 
     
     
         47 . The device of  claim 46 , wherein the ferroelectric particles comprise BaTiO3 or SrTiO3. 
     
     
         48 . The device of any of  claim 41 or 44-47 , wherein the first electrode and the second electrode include ferroelectrics. 
     
     
         49 . The device of any of  claims 40-48 , wherein the device comprises: a first electrode and a temperature sensor on one surface of a first patch; a second electrode and a temperature sensor on one surface of a second patch; and a signal generator electrically connected to the first electrode and the second electrode, wherein the signal generator is configured to generate an electric field between the first electrode and the second electrode so as to change orientations of nanoparticle probes in the pluripotent stem cell, each of the first and second temperature sensors measures a temperature around the pluripotent stem cell, the signal generator is configured to change the intensity of the electric field on the basis of the measured temperature, and division of the pluripotent stem cell is suppressed according to the changed orientations of the nanoparticles. 
     
     
         50 . The device of  claim 49 , wherein the nanoparticle probes comprises a nanoparticle, a plurality of biomarkers attached to the nanoparticle particle, wherein the biomarkers may target the pluripotent stem cell and a passivation film coated on the nanoparticle. 
     
     
         51 . The device of any of  claims 49-50 , wherein the nanoparticle probes can move inside the pluripotent stem cell by the electric field. 
     
     
         52 . A device comprising: a signal generator; a first electrode and a second electrode which face each other; a third electrode and a fourth electrode which face each other; and a temperature sensor electrically connected to the signal generator, wherein the first electrode and the second electrode receive a first AC voltage from the signal generator, the third electrode and the fourth electrode receive a second AC voltage from the signal generator, the signal generator generates a first electric field between the first electrode and the second electrode so as to change the orientation of a nanoparticle inside a pluripotent stem cells, the signal generator generates a second electric field between the third electrode and the fourth electrode so as to change an orientation of polar molecules inside the cancer cell, and the first electric field and the second electric field have mutually different frequencies. 
     
     
         53 . The device of  claim 52 , wherein the nanoparticle is a conductive nanoparticle. 
     
     
         54 . A device comprising: a signal generator; a first electrode and a second electrode which face each other; a third electrode and a fourth electrode which face each other; and a temperature sensor electrically connected to the signal generator, wherein the first electrode and the second electrode receive a first AC voltage from the signal generator, the third electrode and the fourth electrode receive a second AC voltage from the signal generator, the signal generator generates a first electric field between the first electrode and the second electrode so as to change the orientation of a nanoparticle inside a pluripotent stem cells, the signal generator generates a second electric field between the third electrode and the fourth electrode so as to change an orientation of polar molecules inside the cancer cell, and the first electric field and the second electric field have mutually different frequencies. 
     
     
         55 . The device of  claim 54 , wherein the nanoparticle is a nonconductive nanoparticle. 
     
     
         56 . The device of any of  claims 54-55 , wherein the nonconductive nanoparticles are ferroelectric nanoparticles. 
     
     
         57 . The device of  claim 56 , wherein the ferroelectric particles have diameters of greater than about 0 nm to ≤about 50 nm. 
     
     
         58 . The device of  claim 57 , wherein the ferroelectric particles comprise BaTiO3 or SrTiO3.